Theoretical Investigations of the Influence of Pressure on the Selectivity of the Michael Addition of Diphenylmethaneamine to Stereogenic Crotonates

Abstract

SIBFA (sum of interactions between fragments ab initio computed) molecular mechanics systematics has been modified to take into account the effect of pressure on intra- and intermolecular energies. The van der Waals radii are related to the pressure, using Bridgman results on the variation of crystal volume, on one hand, and the relation between the volume of an atom and its van der Waals radius on the other. This procedure produces a decrease of the volume of the systems considered. The modified systematics is used for the study of the conformation at 1 atm and 15 kbar of two stereogenic crotonates and of the complexes formed by these two molecules with the diphenylmethaneamine and the three solvent molecules present in the experiment. The results obtained show that in the case of NMECC 1a the diastereoselectivity induced by high pressure and by the presence of methanol proceeds from an important stabilization of the pro-R reactive complex in which the crotonate has a stacked-transoid conformation. This stabilization is mainly due to intermolecular interactions. In the case of the second crotonate considered, NMCC 1b, our results indicate that pressure induces a stabilization of the pro-R and pro-S complexes having the axial conformation for which the reaction exhibits little diastereoselectivity in qualitative agreement with experimental data. This study tends to show that it is possible to account theoretically for the influence of pressure on molecular conformation and/or complex structure, using a molecular mechanics method that is able to take into account the variation of volumes of the different entities present in the system studied.

Direct Access to Cumbersome Aminated Quaternary Centers by Hyperbaric Aza‐Michael Additions

“…The anti diastereomer could then arise either from the pseudoaxial arrangement of R or from an intermolecular protonation (by the solvent) guided by the nitrogen lone pair, pointing syn to the R group. Note that the importance of the methanol–amine interaction during the process of the aza‐Michael addition has been highlighted in a fine theoretical study by Giessner‐Prettre, Dumas, and co‐workers 15…”

Relating atomic energy, radius and electronegativity through compression

“…, ref. 55 ). The only explicit and systematic experimental estimates of atomic radii at higher pressures that we are aware of are by Royce, who used the Wigner–Seitz definition to evaluate a selection of (metallically) bonded elements.…”

Solvation effects drive the selectivity in Diels–Alder reaction under hyperbaric conditions

“…22 Later, Dumas et al have studied an aza-Michael addition via an atomistic model where the effect of pressure was included modifying the van der Waals radii. 23 More recently, Hoffmann, Cammi and coworkers have studied the effect of pressure from a quantum chemistry approach coupled with an implicit solvation model on a set of organic reactions. 24 The activation volumes was thus evaluated from electronic densities.…”